Periodic Reporting for period 1 - DNA-bots (Enzyme-powered DNA nanorobotic devices)
Reporting period: 2019-04-01 to 2021-03-31
Despite the recent and exciting advances in nanomedicine, only 0.7% of newly developed carriers reach their target locations in vivo, demanding for innovative solutions. One alternative to improve the targeting capacity of nanocarriers is inspired by biological swimmers and machines that abound in nature. The design of “intelligent” artificial systems able to self-propel (swim) in biological fluids and perform complex tasks such as sensing and delivering a cargo on-demand could revolutionize the field. Enzyme-powered nanorobotic devices are able to self-propel thanks to the conversion of a substrate into products, mediated by enzymes, offering high versatility and biocompatibility. A step forward in the field is to control the spatial configuration of enzymes and study its effect in motion behavior, as well as the incorporation of multiple functionalities. In this regard, DNA can offer unique properties as scaffold material for the fabrication of nanostructures, such as site-specific functionalization, sensing and drug delivery, which have been extensively studied by the Host group, led by Prof. Ricci at the University of Tor Vergata (UTOV, Italy). In this proposal, we aim at combining both enzyme-propulsion and DNA nanotechnology to create a new class of biocompatible and biodegradable nanorobotic devices with advanced functionalities including motion, sensing and smart cargo loading and release.
The results arising from this proposal could significantly contribute to the advancement of scientific knowledge in different disciplines, spanning from chemical engineering to synthetic biology and nanomedicine. Particularly, the development of new nanosystems capable of navigating across biological tissues and perform complex tasks could lead to the development of future biomedical tools, with improved target tissue accumulation, penetration and on-demand drug delivery, resulting in diminished off-target effects and maximized therapeutic efficacy. This would result in more efficient therapies with diminished side effects, therefore reducing costs and improving the quality of life of patients.
Motivated by the above arguments, the main goal of this proposal is to combine the unique versatility and tunability of enzyme-propulsion and DNA technology for the fabrication of biocompatible and biodegradable nanorobotic devices with sensing and actuating capabilities.
The results arising from this proposal could significantly contribute to the advancement of scientific knowledge in different disciplines, spanning from chemical engineering to synthetic biology and nanomedicine. Particularly, the development of new nanosystems capable of navigating across biological tissues and perform complex tasks could lead to the development of future biomedical tools, with improved target tissue accumulation, penetration and on-demand drug delivery, resulting in diminished off-target effects and maximized therapeutic efficacy. This would result in more efficient therapies with diminished side effects, therefore reducing costs and improving the quality of life of patients.
Motivated by the above arguments, the main goal of this proposal is to combine the unique versatility and tunability of enzyme-propulsion and DNA technology for the fabrication of biocompatible and biodegradable nanorobotic devices with sensing and actuating capabilities.
In this project, we have worked on the combination of Enzyme Catalysis and DNA Nanotechnology to develop a new class of bioengineered smart nanobots capable of moving and interacting with their environment, with potential applications in biomedicine. First, we have been working on the design and synthesis of full DNA nanobots by using self-assembly approaches, where we demonstrated that these nanostructures are able to move thanks to the use of enzyme catalysis. Then, we explored how enzyme localization affects to the motion of enzyme-powered nanomotors by using different types of chassis (i.e. liposomes and metal organic framework structures). Later on, we have studied the integration of responsive DNA-based approaches for the dynamic assembly/disassembly of catalytic micromotors and finally, we developed synthetic DNA translators for the control of dynamic nucleic acid networks using proteins. Alltogether, the results have lead to the publication of five scientific articles in international peer-reviewed journals, which are accessible to the fulfils with European and National legislation and ensures the free-of-charge online access to its
publication. The results have been disseminated also in different scientific congresses and seminars in the form of oral and poster presentations. The achievements of the proposal have been also disseminated in twitter and have received the attention of the media (national newspapers). Moreover, this project has recently been highlighted in the Horizon Magazine. During the curse of this project, the Applicant has acted as a Marie Curie Ambassador, where she actively participated in organizing a Marie Curie day at the University of Tor Vergata, where her experience as a Marie Curie fellow was shared to young undergraduate, PhD students and early-stage Post-doctoral researchers.
publication. The results have been disseminated also in different scientific congresses and seminars in the form of oral and poster presentations. The achievements of the proposal have been also disseminated in twitter and have received the attention of the media (national newspapers). Moreover, this project has recently been highlighted in the Horizon Magazine. During the curse of this project, the Applicant has acted as a Marie Curie Ambassador, where she actively participated in organizing a Marie Curie day at the University of Tor Vergata, where her experience as a Marie Curie fellow was shared to young undergraduate, PhD students and early-stage Post-doctoral researchers.
The outcomes of this proposal represent a step beyond the state-of-the-art and could likely pave the way towards a new field with huge potential for many scientific areas, including biosensing, nanorobotics, chemical engineering, synthetic biology and biomedicine. The possibilities offered by the rational design and manufacturing of hierarchical nanoarchitectures using synthetic DNA will provide new possibilities to study the influence of fundamental parameters on the design of enzyme-propelled swimmers, which is not possible with the current micro- and nanofabrication technologies. In turn, we have demonstrated that the active motion generated by enzyme-propulsion can provide DNA-based nanomachines with unique capabilities, which may boost their performance for many applications, such as a controlled transport of cargoes or the simultaneous sensing while moving. Furthermore, when intended as smart drug delivery carriers, their propulsive force could increase their performance at overcoming biological barriers and their sensing capabilities could be used as a tool for medical imaging and theranostics. In summary, the unique synergy between the versatility of DNA and enzymes will provide a toolbox of smart micro-/nanomachines able to perform multiple and complex tasks that have not been achieved.